Occurrence of Gastrointestinal (GI) Side Effects upon GLP-1 Receptor Agonist (GLP-1RA) Initiation with Concomitant Metformin Use

GI symptoms are common side effects reported with both GLP-1RA and metformin use, yet these agents are often prescribed in combination. GLP-1RA are initiated at low dose and escalated to minimize the occurrence of GI side effects. Still, most treatment related GI adverse events occur during the dose titration period. We evaluated whether concomitant metformin use increases the rate of GI adverse events during the GLP-1RA titration period. Using data from 4 clinical trials, LEADER (1.8 mg liraglutide), STEP-2 (1/2.4 mg semaglutide), SUSTAIN-6 (0.5/1 mg semaglutide), and PIONEER-6 (14 mg oral semaglutide), we compared the incidence of GI adverse events during the titration period defined as the expected time to steady state of the respective drug (3 weeks-5 months, see table) in participants with and without concomitant metformin use. Of the 16,996 participants in these trials, 12,928 (76%) were treated with metformin. The percent of participants who developed new or serious GI adverse events during the titration period was similar across those with or without concomitant metformin use in each group (GLP-1RA or placebo) in all trials (Table). The occurrence of individual GI event (nausea, vomiting, diarrhea, and constipation) was also similar (data not shown). In summary, concomitant metformin use does not increase the occurrence of GI symptoms during early GLP-1RA treatment. Disclosure K.R.Klein: None. K.K.B.Clemmensen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. E.Fong: Employee; Novo Nordisk A/S. S.Olsen: None. T.J.Abrahamsen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S, Genmab A/S. I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp & Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim.